Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions
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Abstract
Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.
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- Authors
- Koppers, M., Özkan, N., Nguyen, H. H., Jurriens, D., McCaughey, J., Nguyen, D. T. M., Li, C. H., Stucchi, R., Altelaar, M., MacGillavry, H. D., Kapitein, L. C., Hoogenraad, C. C., & Farías, G. G.
- Affiliations
- Utrecht University (NL)
- Genentech (US)
- Corresponding author
- Koppers, Max
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 59
- Issue
- 16
- Pages
- 2053-2068.e9
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC11338522
- OpenAlex
- W4399123356
- Cited by
- 44
- References
- 81
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 7 · 2023: 1 · 2022: 1
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- VU Research Portal (submittedVersion, other-oa)
- Funders
- ERC (ERC-CoG 617050, ERC-CoG 819219, ERC-StG 950617)
- EMBO
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.VENI.202.113, ALTF 741-2020)
- European Research Council (0.16)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- ER tubules, ribosome distribution, axon development, axon morphology, hippocampal neurons, neuronal development
- MeSH terms
- Animals, Axons, Carrier Proteins, Cells, Cultured, Endoplasmic Reticulum, Hippocampus, Humans, Neurons, Ribosomal Proteins, Ribosomes, RNA, Messenger, Protein Biosynthesis, Rats
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